Siriwardana Gamini, Seligman Paul A
Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado School of Medicine, 12700 E. 19th Avenue, Room 9122RC 2, MS B170, Aurora, 80045, Colorado.
Physiol Rep. 2013 Dec 6;1(7):e00176. doi: 10.1002/phy2.176. eCollection 2013 Dec 1.
Studies have presented evidence that besides the well described S phase block, treatment of cancer cell lines with the iron chelator deferrioxamine (DFO) also results in an earlier block in G1 phase. In this article, measurements of cell cycle regulatory proteins define this block at a very specific point in G1. DFO treatment results in markedly decreased cyclin A protein levels. Cyclin E levels that accumulate in early to mid-G1 are increased in cells treated with DFO as compared to the resting cells. The DFO S phase block is shown after cells are arrested at G1/S by (aphidicolin) then released into DFO. The same S phase block occurs with DFO treatment of a neuroblastoma cell line relatively resistant to the G1 DFO block. These experiments clearly differentiate the S phase DFO block from the earlier block pinpointed to a point in mid-G1, before G1/S when cyclin E protein increases but before increased cyclin A synthesis. Apoptosis was observed in cells inhibited by DFO at both cell cycle arrest points.
研究表明，除了已充分描述的S期阻滞外，用铁螯合剂去铁胺（DFO）处理癌细胞系还会导致更早的G1期阻滞。在本文中，对细胞周期调节蛋白的测量将这种阻滞定义在G1期的一个非常特定的点上。DFO处理导致细胞周期蛋白A的蛋白水平显著降低。与静息细胞相比，在G1早期至中期积累的细胞周期蛋白E水平在经DFO处理的细胞中有所增加。在用阿非科林将细胞阻滞在G1/S期然后释放到DFO中后，显示出DFO的S期阻滞。用DFO处理对G1期DFO阻滞相对耐药的神经母细胞瘤细胞系时，也会出现相同的S期阻滞。这些实验清楚地将S期DFO阻滞与更早的阻滞区分开来，更早的阻滞定位在G1中期的一个点上，在G1/S期之前，此时细胞周期蛋白E蛋白增加，但在细胞周期蛋白A合成增加之前。在两个细胞周期阻滞点被DFO抑制的细胞中均观察到凋亡。
